Institute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, Germany.
PLoS One. 2011;6(7):e22814. doi: 10.1371/journal.pone.0022814. Epub 2011 Jul 26.
The aim of this study was to examine postnatal islet and beta-cell expansion in healthy female control mice and its disturbances in diabetic GIPR(dn) transgenic mice, which exhibit an early reduction of beta-cell mass. Pancreata of female control and GIPR(dn) transgenic mice, aged 10, 45, 90 and 180 days were examined, using state-of-the-art quantitative-stereological methods. Total islet and beta-cell volumes, as well as their absolute numbers increased significantly until 90 days in control mice, and remained stable thereafter. The mean islet volumes of controls also increased slightly but significantly between 10 and 45 days of age, and then remained stable until 180 days. The total volume of isolated beta-cells, an indicator of islet neogenesis, and the number of proliferating (BrdU-positive) islet cells were highest in 10-day-old controls and declined significantly between 10 and 45 days. In GIPR(dn) transgenic mice, the numbers of islets and beta-cells were significantly reduced from 10 days of age onwards vs. controls, and no postnatal expansion of total islet and beta-cell volumes occurred due to a reduction in islet neogenesis whereas early islet-cell proliferation and apoptosis were unchanged as compared to control mice. Insulin secretion in response to pharmacological doses of GIP was preserved in GIPR(dn) transgenic mice, and serum insulin to pancreatic insulin content in response to GLP-1 and arginine was significantly higher in GIPR(dn) transgenic mice vs. controls. We could show that the increase in islet number is mainly responsible for expansion of islet and beta-cell mass in healthy control mice. GIPR(dn) transgenic mice show a disturbed expansion of the endocrine pancreas, due to perturbed islet neogenesis.
本研究旨在探讨健康雌性对照小鼠出生后胰岛和β细胞的扩张及其在 GIPR(dn)转基因小鼠中的紊乱，后者表现出β细胞质量的早期减少。使用最先进的定量体视学方法检查了 10、45、90 和 180 天龄的雌性对照和 GIPR(dn)转基因小鼠的胰腺。在对照小鼠中，总胰岛和β细胞体积以及它们的绝对数量在 90 天之前显著增加，此后保持稳定。对照小鼠的平均胰岛体积在 10 至 45 天之间也略有但显著增加，然后直到 180 天保持稳定。胰岛新生的指标，即分离的β细胞的总体积，以及增殖（BrdU 阳性）胰岛细胞的数量在 10 天龄的对照中最高，并在 10 至 45 天之间显著下降。在 GIPR(dn)转基因小鼠中，与对照相比，10 天龄时胰岛和β细胞的数量显著减少，由于胰岛新生减少，总胰岛和β细胞体积没有发生出生后扩张，而早期胰岛细胞增殖和凋亡与对照小鼠相比没有变化。GIPR(dn)转基因小鼠对药物剂量 GIP 的胰岛素分泌得到保留，并且对 GLP-1 和精氨酸的血清胰岛素与胰腺胰岛素含量的反应在 GIPR(dn)转基因小鼠中明显高于对照。我们可以表明，胰岛数量的增加主要负责健康对照小鼠胰岛和β细胞质量的扩张。GIPR(dn)转基因小鼠由于胰岛新生紊乱，表现出内分泌胰腺扩张紊乱。
